Method and device for non-destructive analysis of perforations in a material

ABSTRACT

Method for fabricating and inspecting small holes in a material are disclosed. The method includes directing light onto the material and through the holes formed in the material, and then collecting the light passing through the holes in the material onto a detector. The methods further include analyzing the light for properties of the holes, and modifying the process based these detected properties.

FIELD OF THE INVENTION

The invention relates generally to methods of non-destructive analysis.More particularly, the invention relates to a method and device forquickly and non-destructively analyzing an array of small holesprecisely placed in a material such as a thin film.

BACKGROUND OF THE INVENTION

In different areas of technology it is desirable to make use of a thinsheet of material which has an array of regularly spaced, very smallholes therein. For example, such might be used in the manufacture ofvarious electronic components. Thin sheets which have one or more holesin them could also be used in the formation of components used in inkjet printers or fuel injectors. A more direct application of such a porearray is as a filter. The pore size and pore density could be adjustedto wide range of filter applications. Alternatively, liquid formulationscontaining a drug could be moved through such a porous member to createan aerosol for inhalation.

One of the gentlest and most acceptable methods of administering anagent to a patient is via aerosol. Aerosol therapy can be accomplishedby aerosolization of a formulation (e.g., a drug formulation ordiagnostic agent formulation) and administration to the patient, forexample via inhalation. The aerosol can be used to treat lung tissuelocally and/or be absorbed into the circulatory system to deliver thedrug systemically. Where the formulation contains a diagnostic agent,the formulation can be used for diagnosis of, for example, conditionsand diseases associated with pulmonary dysfunction.

In general, aerosolized particles for respiratory delivery must have adiameter of 12 microns or less. However, the preferred particle sizevaries with the site targeted (e.g., delivery targeted to the bronchi,bronchia, bronchioles, alveoli, or circulatory system). For example,topical lung treatment can be accomplished with particles having adiameter in the range of 1.0 to 12.0 microns. Effective systemictreatment requires particles having a smaller diameter, generally in therange of 0.5 to 6.0 microns, while effective ocular treatment isadequate with particles having a diameter of 15 microns or greater,generally in the range of 15-100 microns.

U.S. Pat. Nos. 5,544,646, 5,709,202, 5,497,763, 5,544,646, 5,718,222,5,660,166, 5,823,178 and 5,829,435 describe devices and methods usefulin the generation of aerosols suitable for drug delivery. These devicesgenerate fine, uniform aerosols by passing a formulation through anozzle array having micron-scale pores as may be formed, for example, byLASER ablation.

Pore arrays having such small features are difficult and costly tomanufacture. Additionally, the pores must be of high quality anduniformity where they are to be used (1) in manufacturing electroniccomponents; (2) in filter materials; (3) in ink jet printers; (4) infuel injectors; and (5) to create aerosols for delivering therapeuticagents to patients in order to insure that the patients consistentlyreceive the therapeutically required dose. Consequently, there is a needfor a fabrication method and an inspection method which can rapidlymanufacture and analyze porous samples of small dimensions to determinevarious parameters including pore size and pore density, and with theability to adjust such parameters to produce a pore array having highquality and uniform pores.

SUMMARY OF THE INVENTION

Thin films having small holes therein (pore arrays) are inspected ornon-destructively analyzed by (1) shining a light through the pores ofthe sheet (2) detecting light which has passed through the pores and (3)analyzing the detected light in a manner which makes it possible toquickly determine whether the sheet should “pass” inspection based oncriteria such as pore size and pore density. The device used in theinspection must include (1) a light source (2) a light detector and (3)a means for analyzing the detected light. Other components may be andgenerally are present such as light filters and lens for improving theoverall accuracy of the system and a means for moving sheets into andout of position to improve the overall efficiency of the system.

The inspection system of the invention can carry out non-destructiveinspection for the presence of microscopic pores within a thin film anddetermine the characteristics of the pore array including the pore sizeand shape, pore density and overall acceptability of the pore array. Thesystem includes the ability to detect the light transmitted through theholes within the sheet and utilize the detected light information todevelop a relationship between the level of light and the existence,location, size and shape of the hole, i.e., light levels detected fromeach hole-feature can be related to the individual size or shape of thehole. Further, the light levels from an entire array of pores within asheet can be related to the collective average size and/or shapes of theholes. If the pores within the sheet do not meet a required criteria analarm can be triggered at a given threshold level indicating that thepore array being tested does not have an adequate number of holes havingthe desired size and/or shape. Such an evaluation is preferably made onan overall reading of the pore array. More specifically, light is shownon the pore array and allowed to move through the holes to a detector.If the detector does not detect a desired quantity of light, either aninsufficient number of holes has been formed or the holes are ofinsufficient size or shape or some combination thereof. Further, if toomuch light is detected, either the holes are too large, have anundesired shape, or there are too many holes present in the sheet.Falling above or below the detected amount of light triggers an alarmwhich causes the pore array being inspected to be rejected.

The system is capable of being used in connection with a variety ofdifferent pore arrays. The pores can have different sizes or shapes andcan be present on the sheet in a variety of different patterns and poredensities. These different sheets with different patterns and pore sizescan be detected using the same charge-coupled light detector element andprocessed using the same microprocessor unit. If necessary the systemcan utilize a variety of different components including mirrors,rhomboids, wedges, or combinations thereof in order to obtain thedesired results with a given pore array of the same basic components ofthe inspection system.

The inspection system of the invention can be used to check all of thepore arrays produced by a given production system or used to spot-checka certain percentage amount of those pore arrays. Further, the systemcan be integrated into a production system so that sheets are inspectedat a given point before being used in an assembly process to produce acomponent which includes a pore array. When utilized in this manner thepore array need not be removed from the system for inspection purposes.Light transmitted through the pores of the sheet can be detected andused as a trigger to accept or reject the pore array for further use inthe manufacturing process.

The inspection system of the invention may be a part of or used with afabrication system for forming the holes that constitute pore arrays.The fabrication system includes an energy source and an energytransporter for directing the energy from the energy source to one ormore locations on the sheet to be drilled. The energy source, such as afocused LASER light, is used to create the pores in the sheet. The poresmay be formed successively (one pore at a time) or simultaneously(multiple pores at once) or any combination thereof, i.e., fabricating apore array by sequentially fabricating subsets of the array that consistof multiple holes. The same light which is used to form the pores mayalso be used to carry out the inspection, as discussed above, in realtime. As the LASER drills through the sheet, light from the LASER (orpossibly another source) begins to impact the detector. Morespecifically, the LASER light used in order to create the holes can bedetected by the detector and used to determine if the holes have beenmade, made in sufficient size, made with the correct shape, whether thepore density is sufficient, or any other property of the pore array. Thelight may be transmitted through one hole at a time, multiple holes inaggregate, or multiple holes individually.

Further, the present invention may further include an energy feedback orcontrol mechanism for controlling the amount or intensity of energybeing delivered to the sheet and/or for controlling the direction orangle at which the energy is being delivered to the pore array. Thefeedback control mechanism utilizes the output of the detector todetermine whether some property of the light detected has reached athreshold level, e.g. a minimum or maximum energy level indicative ofthe size, shape or number of holes that have been formed within thesheet. For example, if the LASER light used in making the holes in thesheet is detected, the detection of a certain amount, e.g., a thresholdlevel, of light can signal that the holes are sufficiently large or havereached the desired pore size thereby signaling that the LASER lightshould be discontinued in order to prevent the hole from being made toolarge. Alternatively, the intensity, amount, pulse frequency, pulseduration, polarization, wavelength, or any other characteristic of thelight may be modified based on measured parameters of the lighttransmitted through a hole or multiple holes. The LASER light may bemodified to produce a different set of holes than the ones that aretransmitting the power to be analyzed, e.g., the power to an array ofholes may be modified based on the light transmitted through a sub-setof the holes. In this manner it is possible to repeatedly and accuratelyproduce pores of a very small size in a sheet. In accordance with thismethod the detection/inspection components of the invention areintegrated with the controlled LASER. Thus, by this method of theinvention the analysis and manufacture are truly carried outsimultaneously and carried out in a manner which they complement eachother. The method preferably can be carried out to simultaneously drilland analyze two, three or a plurality of holes at the same time.

The present invention rapidly inspects samples for holes or throughfeatures as small as the micron and sub-micron level. This method can beused to inspect previously manufactured samples, or can be integratedinto the manufacturing process in order to allow for concurrentproduction and inspection of samples containing such features. In oneaspect of the invention, an imaging lens is used to reduce the size ofthe image which must be inspected, allowing for more rapid inspectionand requiring a smaller CCD detector and shorter analysis time of thesmaller image.

An aspect of the invention is a method of analyzing a pore array whichinvolves directing light onto a pore array, detecting light passingthrough pores of the sheet and then analyzing the detected light in amanner which determines if the pores of the sheet meet desired criteria.

Another aspect of the invention is a method of analyzing a pore array bydirecting light onto the pore array, detecting light reflecting off ofthe sheet and analyzing the reflected light in a manner such that theanalysis determines if pores of the sheet meet a desired criteria.

Another aspect of the invention is an analysis system which includes ameans for directing light onto a pore array, a means for detecting lightwhich is reflected off of and/or light which passes through pores of thesheet and a means for analyzing either the reflected light and/or thelight passing through pores of the sheet so as to determine if pores ofthe sheet meet a desired criteria.

A preferred aspect of the invention includes a means for moving one porearray after another into position for analysis or moving the systemrelative to the sheets in order to continuously analyze one sheet afteranother.

In another aspect of the invention comprises a film, e.g., a polyimidefilm containing LASER-ablated pores which has been inspected todetermine the number and size of the pores.

In still another aspect of the invention, the light source employedproduces ultraviolet light which is selectively transmitted through thefeatures in the inspected sample.

In still another aspect of the invention, the light used to fabricatedthe pore or pores is detected, and some parameter or parameters of thelight are modified based on some parameter or parameters that aredetected.

In an additional aspect of the invention, a method of producing anaerosolization container comprising an aerosolization nozzle passing theinspection method is provided.

In a further aspect of the invention, a method of producing anaerosolization device comprising such a container is also provided.

An advantage of the invention is that pore arrays can be quickly,accurately and efficiently inspected. Another advantage of the inventionis that the fabricated pore sizes and shapes can be very tightlycontrolled, and smaller features can be achieved, leading to a betterperforming final product.

A feature of the invention is that different types of light sources canbe used and different types of filters can be used and positioneddifferently relative to the sheet being inspected.

Another feature of the invention is that the sheet may be moved relativeto the light source and detector or the light source and/or detector maybe moved relative to the sheet.

These and other aspects, objects, advantages and features of the presentinvention will become apparent to those skilled in the art upon readingthis disclosure and reviewing the drawings forming a part hereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is best understood from the following detailed descriptionwhen read in conjunction with the accompanying drawings. It isemphasized that, according to common practice, the various features ofthe drawings are not to-scale. On the contrary, the dimensions of thevarious features are arbitrarily expanded or reduced for clarity.Included in the drawings are the following figures:

FIG. 1 is a schematic drawing of a system of the present invention usedto inspect samples for the size and number of holes passing through thesample.

FIG. 2 shows optical images from samples which pass inspection followingthe inspection method of the present invention.

FIG. 3 shows optical images of samples which do not pass inspection fromthe inspection method of the present invention.

FIG. 4 is a schematic drawing of another system of the present inventionused to form pores within a sheet and having a feedback controlmechanism for controlling the size and number of pores to be formed.

FIG. 5 is a schematic cross-sectional drawing of a formulation movingthrough the pores of a pore array to create an aerosol.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Before the present methods and systems of detecting and analyzing theholes are disclosed, it is to be understood that this invention is notlimited to the particular methodology and devices described, as suchmay, of course, vary. It is also to be understood that the terminologyused herein is for the purpose of describing particular embodimentsonly, and is not intended to limit the scope of the present inventionwhich will be limited only by the appended claims.

It must be noted that as used herein and in the appended claims, thesingular forms “a,” “an,” and “the” include plural referents unless thecontext clearly dictates otherwise. Thus, for example, reference to “aformulation” includes mixtures of different formulations, reference to“an analyzing means” includes one or more of such means, and referenceto “the method” or “the step” includes reference to equivalent steps andmethods known to those skilled in the art, and so forth.

Where a range of values is provided, it is understood that eachintervening value between the upper and lower limits of that range isalso specifically disclosed. Each smaller range between any stated valueor intervening value in a stated range and any other stated orintervening value in that stated range is encompassed within theinvention. The upper and lower limits of these smaller ranges mayindependently be included or excluded in the range, and each range whereeither, neither or both limits are included in the smaller range is alsoencompassed within the invention, subject to any specifically excludedlimit in the stated range. Where the stated range includes one or bothof the limits, ranges excluding either or both of those included limitsare also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the invention, the preferred methods andmaterials are now described. All publications mentioned herein areincorporated herein by reference to describe and disclose specificinformation for which the reference was cited.

The publications discussed above are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the invention is notentitled to antedate such disclosure by virtue of prior invention.

Definitions

The term “porosity” is used herein to mean a percentage of an area of asurface area that is composed of open space, e.g., a pore, hole, channelor other opening, in a sheet, nozzle, filter or other material. Thepercent porosity is thus defined as the total area of open space dividedby the area of the material, expressed as a percentage (multiplied by100). High porosity (e.g., a porosity greater than about 50%) isassociated (in applications where the pore array subsequently has liquidpassed though it, e.g., aerosolization nozzles, fuel injectors, orfilters) with high flow rates per unit area and low flow resistance. Ingeneral, the porosity of the pore array is less than about 10%, and canvary from about 10⁻⁵% to about 10%. Pore arrays of the invention mayhave any porosity without limitation. Further, a pore array may have anynumber of pores (including one), any pore density, any pore shape, orany pore size. For example, a sheet may have a single pore which canrange considerably in size or have thousands of pores each of whichcould be the same or different in size and range considerably in size.In many applications the area of the material is not well defined, i.e.,the pores may exist only in a small fraction of the sheet. In this case,the porosity will be taken to mean the porosity in the area defined bythe existence of pores, and not of the total area of the sheet.

The term “sheet” as used herein will include any material wherein thepresent process is used to inspect or create a pore or plurality ofpores. In certain embodiments, the sheet is presented as a section of aweb of polymeric material or laminates of polymeric and/or othermaterials, such as metals. The sheet material may be hydrophobic and mayinclude materials such as polycarbonates, polyimides, polyethers,polyetherimides, polyethylene and polyesters and the like. Other usefulmaterials include non-polymeric, relatively rigid materials, such asmetals, glasses or ceramics. For inspection applications the sheet mayhave the pores formed therein by any suitable method including LASERdrilling or anisotropic etching through a thin film of metal or othersuitable material. When used as a nozzle, e.g., for aerosol drugdelivery, the sheet preferably has sufficient structural integrity sothat it is maintained intact (will not rupture) when subjected to forcein the amount up to about 40 bar, preferably of up to about 50 bar whilethe formulation is forced through the pores. In the preferredembodiment, the sheet is presented as a section of a web of polymericmaterial or laminates of polymeric and/or other materials, such asmetals. However, the sheet is in general not limited to planargeometries. It would be obvious to one skilled in the art that thepresent invention may be applied to many geometries, metal parts used infuel injection systems, or numerous other applications

The term “pitch” as used herein generally refers to a sheet ormultiplicity of sheets positioned in a single positioning operation forinspection and/or pore array fabrication. In the preferred embodiment, apitch consists of an area or multiplicity of areas on a polymeric orlaminate web. A pitch can include any number of sheets, but preferablyincludes from 1 to about 10 sheets, and more preferably includes fromabout 4 to about 8 sheets, and most preferably includes about 6 sheets.

The term “pore array” will be interpreted to mean any sheet having oneor more holes therein. However, there are a number of types of preferredpore arrays which the system and method of the invention areparticularly useful for producing and/or inspecting. Thus, the porearray may mean a sheet of material having any given outer parametershape (may have a planar or a convex shape), wherein the sheet has onepore or a plurality of pores therein, which openings may be placed in aregular or irregular pattern, and which pores have an unflexed diameterof their exit aperture in the range of about 0.01 micron to about 100microns and a pore density in the range from about 1 to about 1,000pores per square millimeter for respiratory delivery. When the porearray is an array of nozzles for ocular delivery, the pores have anunflexed diameter of their exit aperture in the range from about 5microns to about 50 microns, preferably from about 7.5 to about 25microns, and a similar pore density. The nozzle array has a porosity ofabout 0.0001% to about 0.2%, preferably about 0.001% to about 0.1%. Inone embodiment, the nozzle array comprises a single row of pores on,e.g., a large piece of sheet material. The pores may be cylindersperpendicular to the surface of the sheet, or may have a conical orother shape.

The terms “detector”, “light detector” and the like are usedinterchangeably and will be interpreted herein to any device used tomeasure any property of incident light, including but not limited toenergy, power, amplitude, phase, polarization, wavelength, beam width,radius of curvature, coherence, or propagation direction. Examples ofdetectors include imaging detectors such as CCD arrays, non-imagingdetectors such as semi-conductor, bolometer, pyroelectric orthermoelectric detectors, or other device or material. Although it ispreferable that the detector convert incident energy into electriccurrent, it could also be possible to use mechanical means or othermeans of controlling process parameters based on properties of incidentlight.

General Overview

The invention provides a method of rapidly inspecting and analyzingmultiple holes or through features present in a sample. The methodcomprises directing a light source producing a wavelength of light whichis absorbed by the sample material, but which passes through the holesor through features and is detected by a light detector, for example acharge-coupled device. An imaging lens can be used to reduce the size ofthe image, thereby reducing analysis time and increasing throughput.This inspection method can be integrated into the manufacturing of porearrays for a variety of uses.

FIG. 1 is a view of a schematic representation of the inspection systemof the invention. The light source 1 is chosen based on a variety ofcriteria relating to factors such as how the wavelength of light emittedby the source will be effected by the material of the sheet 10 beinginspected. Light from the source 1 may shine directly on the sheet 10but is preferably directed through a light guide 2, e.g., optical fiberor optical fibers.

Light emitted from the light guide 2 may shine directly on the sheet 10but is preferably directed through all or any of an optical diffuser 3,illuminated lens 4 and one or more spectral filters 5.

The light exiting the spectral filters 5 shines on the pore array 10.Substantially all if not all of the light striking the sheet is eitherabsorbed or reflected and therefore does not travel through the sheet 10unless the light enters one of the pores of the pore array. Lightentering a pore is partially transmitted and strikes the light detector8, which is preferably in the form of a charge-coupled device (CCD).Before contacting the light detector 8 the light may pass through animaging lens 6 and an aperture stop 7. Once a pore array 10 has beeninspected it is preferable to simply rotate a cylinder 11 containing newpore arrays and wind up the inspected pore arrays on the cylinder 12. Inthis manner one pore array after another can be inspected therebyproviding an efficient inspection system.

All of the light exiting the pores of the pore array 10 is preferablycontained within a light containment tube 13. This allows for animproved signal and also improves the stray light which might effect thesignal on the light detector 8. After light has been detected on thelight detector 8 the signal obtained is transmitted to a microprocessor9 which carries out computer image analysis. The processing can becarried out in a variety of different ways and can focus on individualpores of the sheet or, more preferably, on the total signal received. Ifthe total signal received is too small then the pores are insufficientlylarge, incorrectly shaped, or present in an insufficient pore density.If the signal received is too large than the pores are too large, areincorrectly shaped, or are present in an excessive pore density.Regardless of the criteria set once an analysis is made then the systemprovides a signal as to whether the pore array being inspected passesinspection or should be rejected.

System Components

The basic components of the system are shown in FIG. 1. However, ofthese components it is necessary to include the light source 1,detection means 8 and analyzing means 9. Analyzing means 9 is preferablya microprocessor, but could also be a discrete electronic controller, ora mechanical controller. The other components are preferably used inorder to increase the accuracy and efficiency of the system. Mostimportantly, the system preferably includes a means for moving one ormore sample sheets 10 after another into position for inspection orsimultaneous fabrication and inspection. Each of the components as shownin FIG. 1 will now be described in further detail.

FIG. 5 shows the pore array 10 in place. The formulation 20 is in acontainer 21 and moves through a channel 22 to exit as an aerosol 23.This container 10 with the pore array 23 is disclosed within U.S. PatNo. 5,823,178.

The illumination light source 1 can be a commercially purchased lightsource sold under the trade name Ultracure 100SS Plus. The light sourceis a 100 watt mercury lamp system typically used in UV-curingapplications. Mercury lamps typically emit strong spectral components atabout 365 nm which is strongly absorbed by polyimide film having athickness of 25 microns which film is sold by DuPont under the tradename Kapton. The light source does emit spectral peaks in the 300-400 nmrange and has a useful spectral range of light of wavelengths less than450 nm. The light having a wavelength of less than 450 nm is absorbed inthe top few microns of the film which is 25 microns thick. Wavelengthslonger than 550 nm are not absorbed at all but would be transmittedthrough the film. The combination of illumination and wavelengthabsorbed by the film determines the contrast between light transmittedthrough the film and light transmitted through the holes. Films can beused where all of the light is absorbed. Further, detectors can be usedwhere wavelengths of light which pass through the film are not detectedby the detector 8. The greater the contrast produced between lightpassing through the pores and light passing through the film, the morerobust the image processing algorithms for image analysis.

Although essentially any type of light source can be used arc lamps arepreferred and are characteristically small sources of light which enablemore efficient focusing and collimation of the light. This makes itpossible to transmit light into a light guide and also makes it possibleto obtain relatively good collimation of the light emitted from thelight guide. Collimated light on the inspection sample insures that theilluminated incident light is at the same angle for each hole in thefilm. If light were shown on the film at an angle this could providedistorted signals in that some signals entering the holes in the film atthe beginning might not exit even though the hole was completely throughthe film. This would create an error which error would be enhanced asthe film became thicker and/or the angle of the light increased. Othersources of light may clearly be used, so long as they are of awavelength that can be transmitted through the desired pore, but aresubstantially blocked by the sheet.

A light guide such as the one sold under the trade name Lumatec may beused with the system of the present invention. Such a light guide hasabout a 5 mm core diameter and about a 1000 mm length. The light guideis selected due to its ability to transmit light of a wavelength in therange of about 300 to about 400 nm. The light guide assists in makingthe beam uniform at its exit face due to multiple bounces mixing rayswithin the fiber core guide region. The light guide ensures that thesame amount of illuminating light is incident on each hole of the film.If a light source emits a uniform beam without a light guide the lightguide could be eliminated. The mechanical flexibility and length oflight guide provide additional degrees of freedom in order to addressremote areas without the need for mirrors and relay lenses needed toobtain a free beam optical path. The light guide also makes it possiblefor the light source to be located at a distance away from theinspection area. This is a desirable feature although not a requirement.

It is also preferable to include an optical diffuser 3. The diffusercontributes to the uniformity of the beam on exiting the fiber. Thediffuser consists of glass with gentle ripples on the surface on eachside. Although the diffuser is not necessary some improvements in theaccuracy of readings obtained could be expected by the use of adiffuser. A particularly preferred diffuser is the Coherent-Ealing glassdiffuser.

The system also preferably includes an illuminating lens 4. Aparticularly preferred lens is sold under the name Melles-Griot which isa plano-convex, synthetic fused silica lens having a focal length of 25mm. The lens collimates the beam coming from the light guide and directsthe beam to the sample being inspected. It is also preferably to utilizespectral filters 5. Two spectral filters preferably used are sold underthe trade name Schott Color Filter UG-11 and Schott Color Filter KG-3.This combination of spectral filters selects a 300 to 400 nm spectralband to be utilized for the inspection application for the holes on aKapton film of the type described above. The UG-11 essentially blocks avisible portion and the KG-3 blocks the infrared portion resulting in UVbeing transmitted through the filtered combination. These transmissionfilters or a more suitable spectrally selected mirror could be anintegral part of the illumination source precluding the need forexternal filters.

Different filters or combinations of filters can be used in order toblock light that might be transmitted through the sheet even though apore is not present. Accordingly, such a filter or group of filterscould be placed at any desired position between the light source anddetector including immediately in front of the light source (i.e.,before the pore array) or immediately in front of the light detector.Provided the material of the sheet is comprised of material which is nottransparent to any of the light then the filters are not necessary.However, when the sheet is particularly thin (as is often the case) andcomprised of polymer materials (as is often the case) light istransmitted or at least some wavelengths of light are transmitted.Accordingly, to obtain accurate readings the filters are used to filterout the light that would be transmitted through the sheet even though apore is not present.

Light passing through the pore array may pass directly onto the lightdetector 8. It is preferable that the light first pass through animaging lens. A suitable imaging lens is sold under the trade nameMelles-Griot symmetric-convex fused silica lens. This lens has a focallength of about 50 mm. The imaging lens focuses the light transmittedthrough the pore array to the detection element 8. The lens is nothighly corrected for lens aberrations due to cost considerations. Customlens designs could be utilized but would be more costly thancommercially available lenses. Further, many of the different lensmaterials utilized in custom lens designs do not transmit ultravioletlight with high efficiency. Accordingly, simple and cost-effectivesolution was the selection of the simple single element lens which isheld within the light containment tube 13.

After passing through the imaging lens 6 the light preferably passesthrough an aperture stop 7. A useful aperture stop is a variable irissold by Thorlabs. The aperture stop is used to sharpen the resolution asneeded. The smaller the aperture the greater the ability to reduce theeffects of lens aberrations. Thus, the aperture is needed less if thelens includes no aberrations. By closing the aperture down it ispossible to sharpen the image. This is especially useful for imaginglenses that are not corrected for off-axis rays such as the singleelement lenses described above.

After passing through the aperture 7 and the light contacts the lightdetection element 8. A useful light detector is sold by Sony and is ablack and white CCD sold as model XC-75CE. The detection element istypically a standard charge-coupled device (CCD) of the type used incameras which capture a two-dimensional image and allow computer imageprocessing to be performed on the signal detected. A typical CCD is thetype used in an eight-bit camera having 256 gray levels available perpixel. Cameras with greater or lesser than eight bits may also be used.A typical CCD chip in a camera has a size of about 4.8 mm vertically andabout 6.4 mm horizontally containing 439,992 pixels. Each of the pixelsis about 8.6 microns wide by about 8.3 microns vertically and there are756 pixels horizontally and 582 pixels vertically. The configurationdescribed here is a common CCD configuration used in cameras andprovides a cost effective system. When the imaging lens is located forunity magnification: (1:1 imaging) the area which can be inspected isequal to the active area of the detection element. At this magnificationit is possible to separate the bright spots in the image by a distanceof approximately 5 pixels. If there are less than 5 pixels betweenbright spots the spots begin to blur together and the ability tocorrectly count the number of holes is compromised.

The information obtained from the detector 8 is forwarded to themicroprocessor 9. A useful image acquisition and processing unit isCheckpoint 900C by Cognex. The frame grabber is a computer expansionalelectronics board which converts the image signal from the lightdetector 8 to a digital array of numbers consisting of gray levels andtheir pixel location in the two-dimensional image. This makes itpossible for computer processing of the array of numbers (imageprocessing). Blob analysis is a typical image-processing tool which iswidely available commercially. This type of processing detects whethermany bright pixels are adjacent to one another. Then the tool can countwithin the image the number of Blobs that are above a pre-specifiedthreshold. The number of Blobs typically corresponds to the number ofholes in the inspection sample. Another image processing tool whichcould be used is referred to as a “light meter” or “mean pixel value”which sums the gray levels of all of the pixels within a particularpre-specified region of interest (ROI) and calculates the average.

Simultaneous Manufacture And Analysis

The present invention is directed towards analysis of perforations in amaterial. In general, the method is used to scan a pore array whichincludes a plurality of pores and make an analysis as to whether or notthe sheet passes or fails based on an analysis of a plurality of poreswith consideration to a plurality of criteria simultaneously.

The invention is also designed so that pore arrays can be analyzedsequentially.

More specifically, the device for analyzing the sheets can include ameans for holding the sheet in place while it is analyzed and a meansfor moving one sheet after another into an inspection position. Thistype of consecutive inspection/analysis procedure is useful duringmanufacturing. However, this method does not specifically affect themanufacturing other than to indicate that a sheet either passes or failsthe inspection analysis.

In an alternative embodiment the invention can be designed so that itspecifically affects, controls or improves the actualmanufacturing/production process. Pore arrays made with currently knownsystems and techniques produce an average pore size that can varyunacceptably from pore array to pore array, or within a given porearray. For example, in pulmonary delivery of systemically activecompounds, when an aerosol is created through a nozzle, the aerosol sizeis in general related to the size of the nozzle. Control of the poresize thus directly affects control of regional deposition in the lung.This alternative system and method are used to analyze each pore arrayas it is created and to provide feedback to adjust or stop themanufacturing/production process in order to reduce the variability ofthe size, shape, and or number of the pores. Because of this reductionin variability, smaller pores can also be reproducibly manufactured.

The basic components of such a closed-loop feedback system areschematically shown in FIG. 4 with the necessary components including anenergy or LASER light source 20, an energy or light transport system 24,a detection means 28, and a feedback mechanism including an analyzingmeans 32 and feedback control lines 34 and/or 36. As mentioned above,the other components are preferably used in order to increase theaccuracy and efficiency of the system. The system of FIG. 4 functionssimilarly to the system of FIG. 1 with the primary difference being thatthe light source 20 is used both for pore creation and inspection, andthe additional use of a feedback control mechanism to adjust ordiscontinue the pore array manufacturing process (e.g., the delivery oflight to the sheet, the position of the pore array, the temperature,etc.).

The LASER light from energy source 20 may be delivered through anoptional light guide 22, e.g., optical fiber or optical fibers and ispreferably directed through an energy or light transport mechanism 24positioned prior to the sheet (on the entry side of the sheet) whichfinely focuses the LASER light to drill or form pores or holes withinsheet 38. The light transport mechanism may comprise a shutter,homogenizer, mask, and/or projection lens, an optical system well suitedto the use of excimer LASERs. Suitable projection lenses would have alarge field of view, from about 2 mm to about 60 mm, preferably fromabout 5 mm to 45 mms, still more preferably from about 25 to about 40mm. The effective focal length would generally range from about 100 toabout 500 mm, preferably from about 150 to about 350 mm, more preferablyfrom about 200 to about 300 mm. The Numerical Aperture ranges from 0.04to about 2, preferably from about 0.005 to about 1.5, more preferablyfrom about 0.75 to about 1.25. The projection lens is usually a 2× to10× reduction, preferably 3× to 7× reduction and more preferably about a5× reduction. The shutter is in general a mechanical means for shuttingoff the beam and in general needs to stop the beam rapidly, inapproximately 2 to about 25 ms, preferably from about 4 to about 15 ms,more preferably in about 8 ms. These actuation times can be achieved inmany ways, including motors, pneumatics, acousto-optics, and the like,but in the preferred embodiment employ solenoids. Alternatively, thelight transport mechanism may comprise an optional spatial filter, anoptional diffractive element, and a focusing lens, an optical systembetter suited to LASERs such as frequency multipliedYittrium-Aluminum-Garnet (YAG) or similar LASERs. The LASER light may betransmitted in a continuous stream or as discrete pulses depending onthe desired result. Upon formation of a pore, light passes through thepore and is transmitted to and strikes light detector 28 which ispositioned on the opposite side or exit side of sheet 38. As with thesystem of FIG. 1 before contacting light detector 28, the light may passthrough an imaging lens 26 and an aperture stop 27. Alternatively, thetransmitted light may simply fall directly on the detector, in the caseswhere only the total transmitted power is measured, or when the detectoris close enough to the pore array that the light from individual poresis distinguishable. All of the light exiting the pores of the pore array28 is preferably contained within a light containment structure 30 inorder to minimize light from straying which might affect the signal onthe light detector 28. After light detector 28 detects the light, asignal representative of one or more parameter of the LASER light, e.g.,temporal and/or spatial distributions of the light's power or intensitylevel, is transmitted to a feedback control 32 which carries outanalysis of one or more parameters known to be affected by pore size,shape, or density. Based on this analysis, and in particular, based onthe determination as to whether the light parameter is below or above acertain threshold level, a control signal is sent from feedback control32 back to LASER light source 20 and/or to energy transport system 24and/or to tape transport 42 via signal lines 34, 36, and/or 43,respectively. Pore size may be controlled where the threshold levelcorresponds to the optimum pore size. The control signal may be used toturn the energy source 20 on and off or to adjust the energy transportsystem, e.g., vary the power of a continuous light beam or vary thefrequency of pulsed light. For example, where LASER light is provided ina single, continuous pulse, the control signal may involve discontinuingthe pulse. Where the LASER light is provided in a series of discretepulses, the control signal may involve reducing the number, duration, orfrequency of pulses. Reducing the number of pulses to zero, or ending acontinuous pulse, may be achieved by controlling the LASER, or with andexternal shutter. In addition, if the analysis determines that the porearray fails some criterion that cannot be fixed with further processing,e.g., the pores are too large, then the sheet may be marked, removed, orotherwise identified as flawed. Once pores have been satisfactorilyformed within a sheet 38, multiple sheets 38, or a section of sheet 38,the sheet maybe advanced from a formation/inspection position to allowfor formation of additional pores in another sheet, series of sheets, orin another section of the same sheet.

Energy source 20 is preferably a LASER light such as a UV LASER, an IRLASER or a visible light LASER. Examples of UV LASERs that are suitablefor use with the present invention include a Nd:YAG or Nd:YLF frequencymultiplied UV LASER, preferably a solid state diode pumped Nd:YAGfrequency tripled LASER with 2-20 nanosecond pulses emitting light at355 nanometers LASER. Preferably the LASER is an excimer LASER, with awavelenght from about 100 to about 500 nm, preferably from about 193 toabout 350 nm, most preferably from about 248 or about 308 nm. Theprefered chemsities of the excimer LASER are xenon/chlorine orkrypton/florine. The excimer systems are generally pulsed, withrepetition rates of about 50 to about 1000 hz, preferably from about 100to about 400 hz, and most preferably about 300 Hz. An example of asuitable LASER is the Lambda Physik Steel 1000 LASER, although it willbe obvious to one skilled in the art that other LASER systems could beused. Pulse durations are generally in the range of from about 10 toabout 100 ns, preferably from about 15 to about 40 ns, and mostpreferably about 28 ns. Pulse energies will vary based on theapplication, but will be generally in the range of about 1 mJ to about1000 mJ, and for the fabrication of pore arrays in thin polymer filmsthey will be preferably from about 300 to about 800 mJ, most preferablyfrom about 400 to about 600 mJ. The pulse energy incident on the sheetwill range from about 0.01 mJ to about 10 mJ, for the fabrication ofpore arrays in thin polymer films they will be preferably from about 3to about 8 mJ, most preferably 4 to 6 mj. A suitable IR LASER for usewith the present invention is a short (1-100 femtosecond) pulse IR. Itwould be obvious to those skilled in the art to substitute other lightsources and frequency mutliplying schemes as appropriate for the processand materials under consideration

Energy transport system 24 may be a lens system which may include one ormore means for creating one or more focused beams of light characterizedby parameters for the size and shape of the one or more pores or spotsto be formed. Such means may include but are not limited to one or moreof the following: a beam-expander, a final objective/projection lens, aspatial filter, a variable attenuator, a beam splitter for directingenergy at multiple locations at once, or a galvo mirror for rapidlydirectly energy to multiple locations simultaneously. The beam splittermay be based on refraction/transmission interfaces or on diffractiveoptics, or can be split using a homogenizer. Various types ofdiffractive optic beam splitters may be used including but not limitedto those based on a transmission mask, on phase difference optics or onindex of refraction, or a combination thereof, each of which may beeither binary, stepped, or continuously varying. The beam splitter maydivide the beam in one or two directions, providing a few beams (about 4or more) or a large array of dozens or hundreds of beams. The beamsplitter may produce a 1-dimensional array of about 4 to about 100beams, for example, or a two-dimensional array of about 12 to about 1000beams, for example, or multiple copies of the above arrays.

Where multiple pores are being formed, the parameters of the energydirected by energy transporter 24 may be the same and controlled in thesame way for all of the pores or spots, or may be different andcontrolled differently from pore to pore or from spot to spot. The poweror intensity (both temporal and spatial distribution) of the deliveredenergy may be preset such that in one or more regions of the material tobe drilled it is above or below a threshold level, such as for example,the threshold for damage to the material, the threshold for thermalablation of the material, or the threshold for photoablation of thematerial. For many applications, it may be preferable to initiallyselect a power intensity level that produces holes that are smaller thandesired but which can be adjusted as needed to achieve the optimal size.In this way, the risk of forming holes which are too large is minimizedand the cost of rejecting damaged or useless material is reduced. Thetotal amount of energy per pore may vary from application toapplication. Typical ranges for micro-meter scale structures fabricatedusing pulsed UV LASERs suitable for, for example, aerosol drug deliverynozzles in thin polymer films include from about 0.1 to about 5microjoules per pulse, more typically from about 0.2 to about 1microjoule per pulse, and even more typically from about 0.2 to about0.6 microjoule per pulse. The transmitted energy per pulse per pore atthe end of the fabrication process will in general also vary fromapplication to application, depending on for example the size and shapeof the pore, the properties of the light source, and the material of thesheet. Typical ranges for micro-meter scale structures fabricated usingpulsed UV LASERs suitable for, for example, aerosol drug deliverynozzles in thin polymer films include from about 1 femtoJoule to about 1microjoule per pulse, from about 1 femtoJoule to about 1 nanojoule, orfrom about 10 femtoJoule to about 20 picoJoule. The energy density perspot per pore using pulsed UV LASERs in a polymeric material likepolyimide may range from about 0.1 to about 2 Joules/cm² (1 to 20 nJouleper square micrometer), or more typically from about 0.25 to about 0.4Joules/cm² (2.5 to 4 nJoule per square micrometer). As mentioned above,the energy may be delivered continuously or in pulses. If in pulses, thepulses may have any suitable duration, for example, from about 1 toabout 100 nanoseconds, or less than about 1 nanosecond, or less thanabout 1 picosecond.

Detector means 28 which measures some property of the light transmittedthrough the formed hole or holes may comprise a single detectorconfigured to detect the energy passing through some or all of theholes, or may comprise two or more sub-detectors, each configured todetect energy from less than all of the holes. Detector means 28 mayinclude but is not limited to a semi-conductor, bolometer, pyroelectricdetector, thermoelectric detector, down-conversion/photodiode, or otherdevice or material that converts incident energy into electric current.An example of a suitable detector for detecting transmitted power is aHUV-4000B operational amplifier photodiode combination (EG&GOptoelectronics). Another example of a suitable detector for detectingtransmitted power is a Star Tech downconversion/photodiode EnergyDetector, model number XR-16-G. In a preferred embodiment, the beam fromthe LASER is directed toward multiple areas on the sheet, each areabeing a target for the fabrication of an individual nozzle array.Individual target areas each have their own detector, and each detectoris used to cut off the power to each target area using a shutter.Detector means 28 may also be a photo-diode or charge-coupled (CCD)device. Detector 28 may include an optical input filter which isconfigured to pass the particular drilling wavelengths of the LASERlight and to reject other wavelengths, thus increasing the sensitivityof the detector by eliminating background light. The time constant ofthe detector 28 or the time constant of the electrical output of thedetector 28 may be such that it allows measurement of individual pulseenergy, measurement of the temporal shape of the individual pulses orthe weighted integral of the energy of multiple pulses, or a combinationthereof. The detector 28 may also implement phase-sensitive detection,such as a lock-in amplifier circuit referenced to the pulses of theLASER. The output of detector 28 may be further filtered to improvesignal quality.

The feedback control mechanism uses the output of detector 28 todetermine whether the light being delivered to the pore sites requiresadjustment or if a new sheet or sheets should be moved to the processingposition. In the case of multiple pore sites, this determination mayinclude identifying which of the pore sites require adjustment and whichdo not. The feedback control or adjustment may be achieved by sending acontrol signal via signal line 34 to, for example, turn off the energysource 20 such as when the transmitted energy rises above a thresholdlevel which indicates that the desired hole size has been achieved for aparticular pore site or set of pore sites. For example, the LASER powermay be adjusted or stopped completely when the detector measures anincident power. Alternatively, a control signal sent via signal line 36may be used to adjust the energy delivery system 24 in order to modifyor interrupt the delivery of energy to one or more array sites while theenergy delivered to other array sites is maintained until theirrespective pores achieve the target configuration, e.g., size. One meansfor accomplishing this is to provide as a part of the energy deliverysystem 24 a shutter for each beam or set of beams of LASER lightimpinging on the sheet or for each pore site. The shutter may bepositioned anywhere between the light source and the sheet to bedrilled, but must be down stream of any beam splitting component ifindividual beams or series of beams are to be shut off individually.When some parameter of the transmitted light, preferably the targetenergy level of the LASER light (i.e., the level corresponding to thedesired pore size) passing through the sheet at a particular pore siteor set of pore sites is achieved, the feedback mechanism triggers theshutter to block that particular beam, thereby preventing furtherdrilling of the sheet and enlargement of the hole or holes. Another wayof accomplishing this is by using an adjustable beam attenuator. Yetanother way of accomplishing this is to signal the tape transportmechanism to move to the next sheet or set of sheets to begin drillingthere.

The feedback system may use integrated and filtered outputs from thedetector 28 to determine the appropriate action based on the accumulatedtransmitted energy of one, a few, or all pulses used in the drillingoperation. This determination may include averaging the energy of someor all pore sites either with equal or unequal weighting.

The determination may use exponential weighting as occurs when thedetector time constant is similar to the pulse repetition rate. Thefeedback system may be used, after the determined amount of transmittedenergy is measured, to change some parameter of the process until adifferent transmitted energy level is achieved, or until a certainnumber of additional pulses are delivered, or until some other action isaccomplished or criterion is achieved. The various parameters which maybe controlled include but are not limited to the intensity or power ofthe delivered energy, the pulse rate, the fluence, the focal point ofthe LASER, the pulse duration, and/or the pulse repetition rate

The pores to be formed using the present invention can have any size andshape. For aerosolization nozzles, they have dimensions ranging fromabout 0.1 to about 50 micrometers, preferably about 0.3 to 10micrometers. For pulmonary drug delivery, the pores will in generalrange from about 0.1 micrometer to about 10 micrometer, preferably fromabout 0.3 micrometer to about 2.5 micrometer, more preferably from about0.4 micrometer to about 1.4 micrometer. The pores can have any shape,including roughly conical shapes, cylindrical shapes, or combinationsthereof. The exit of the pore can have any shape, but is preferablyapproximately circular.

The beams delivered to the sheet may have any radial shape including butnot limited to substantially circular and may be characterized by anyappropriate profile including but not limited to roughly gaussian ortop-hat profiles. Any suitable number of pores or holes may be formedincluding from one hole to several hundreds or more.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how tomake and use the present invention, and are not intended to limit thescope of what the inventors regard as their invention nor are theyintended to represent that the experiments below are all or the onlyexperiments performed. Efforts have been made to ensure accuracy withrespect to numbers used (e.g., amounts, temperature, etc.) but someexperimental errors and deviations should be accounted for. Unlessindicated otherwise, parts are parts by weight, molecular weight isweight average molecular weight, temperature is in degrees Centigrade,and pressure is at or near atmospheric.

Example 1

This experiment demonstrates the use of a method of the invention toinspect holes in a sample. A mercury arc lamp of the type commonly usedfor ultraviolet adhesive curing was used for the light source. Theultraviolet portion of the spectrum was specifically isolated betweenabout 300 and 400 nanometers utilizing appropriate reflective andtransmissive optical filter elements well known to those skilled in theart. This ultraviolet portion consisted mainly of the strong emissionline from mercury at 365 nanometers. The filtered light was guided via acommonly used liquid light guide which transmits near ultraviolet in thespectral range selected. At the output of the fiber, a diffusereflectance glass was used to provide additional homogenization of thebeam exiting the guide. A condensing lens was then used to collimate thelight and illuminate the sample to be inspected. The sample was apolyimide film. Spectral filters were located in the collimated light toensure the rejection of any detectable visible and infrared light whichwould transmit through the sample substrate. An imaging lens waspositioned in back of the sample to provide an image onto a lightdetection element. This element was a charge-coupled device or CCD. Inclose proximity to the imaging lens was an aperture stop which, whenclosed down to a small diameter, produced a clearer image at the CCD.The image was displayed on a monitor and the image information storedinto a computer image file. This image was processed in order todetermine the number and size of features in the sample. For example, anozzle with an array of hundreds of through holes appeared on the imageas an array of bright spots. The number of spots in the image shouldcorrespond exactly to the number of holes designed into the part. Theamount of light incident on the CCD from each hole is transformed intogray levels covering picture elements or pixels in the CCD. These graylevels ranged from 0 to 255 for 8-bit CCD cameras. The pixelscorresponding to each hole were defined as a cell, and the sum of thepixel gray levels within each cell was determined and correlated withthe size of the hole. Thus image processing enabled the determination ofboth the number and size of the holes in the array.

Example 2

This experiment demonstrates the use of a method of the invention toinspect holes in a sample. A mercury arc lamp of the type commonly usedfor ultraviolet adhesive curing was used for the light source. Theultraviolet portion of the spectrum was specifically isolated betweenabout 300 and 400 nanometers utilizing appropriate reflective andtransmissive optical filter elements well known to those skilled in theart. This ultraviolet portion consisted mainly of the strong emissionline from mercury at 365 nanometers. The filtered light was guided via acommonly used liquid light guide which transmits near ultraviolet in thespectral range selected. At the output of the fiber, a diffusereflectance glass was used to provide additional homogenization of thebeam exiting the guide. A condensing lens was then used to collimate thelight and illuminate the sample to be inspected. The sample was apolyimide film. Spectral filters were located in the collimated light toensure the rejection of any detectable visible and infrared light whichwould transmit through the sample substrate. An imaging lens waspositioned in back of the sample to provide an image onto a lightdetection element. This element was a charge-coupled device or CCD. Inclose proximity to the imaging lens was an aperture stop which, whenclosed down to a small diameter, produced a clearer image at the CCD.The image was displayed on a monitor and the image information storedinto a computer image file. This image was processed in order todetermine the number and size of features in the sample. For example, anozzle with an array of hundreds of through holes appeared on the imageas an array of bright spots. The number of spots in the image shouldcorrespond exactly to the number of holes designed into the part. Theamount of light incident on the CCD from each hole is transformed intogray levels covering picture elements or pixels in the CCD. These graylevels ranged from 0 to 255 for 8-bit CCD cameras. A region of interestencompassing an entire array of holes is identified. The light metertool is used to determine the average light level transmitted by thearray of holes. This light level corresponds to an average calibratedhole size for the array.

Example 3

This experiment demonstrates the use of a method of the invention toform and inspect spots in a 25 micrometer thick polyimide sheet. Theenergy source used was a frequency tripled niobium yttrium based LASERemitting 355 nm wavelength pulses, each having approximately 0.4 toabout 0.6 microjoule of energy. The LASER was focused on spot having adiameter of about 12 to about 15 micrometer and produced a hole with anexit diameter between about 0.4 and about 0.6 micrometer. The formedhole passed approximately 0.5 to about 10 picojoules which was detectedby a silicone diode detector. Based on the signal from the detector, adiscrete electronic feedback circuit comprising a comparator, areference voltage and logic gates sent an electronic signal to the LASERto stop generating light pulses.

Several sets of pore arrays were fabricated using the same light sourceand optical system drilling one pore at a time. Some arrays wereproduced using a predetermined number of pulses and some using thefeedback system to control the number of pulses used to drill in anattempt to control the size of pores produced. The following dataillustrate the improvement in control of pore size that was achieved bythe implementation of feedback. Each value in “Array Avg. Size” is theaverage size of ten pores within a single array, and “SD, Intra” givesthe standard deviation of these ten pore sizes for each of the arrays.“SD, Inter” is the standard deviation of the “Array Avg. Sizes” valueswithin a session, and the “Session Avg. Size” is their average. The poresize within each nozzle is better controlled, the average pore size ofeach pore array during fabrication session is better controlled, and theaverage pore size of all arrays in a given session is closer to thetargeted size, 595 nm in these cases. All sizes are given in nanometers.

Array Average Array # Size (nm) SD Intra Fabrication Session withoutFeedback 1 550 20 2 613 76 3 631 20 4 631 99 5 603 61 6 586 36 7 617 338 589 52 9 672 75 Session Average Size 610 SD Inter 34 FabricationSession with Feedback 1 597 9 2 583 10 3 589 12 4 590 18 5 598 13 6 59815 7 609 14 8 594 12 9 599 14 10 600 9 11 592 26 Session Average Size595 SD Inter 7 Fabrication Session with Feedback 1 603 16 2 590 9 3 60214 4 591 9 5 586 11 6 597 9 7 578 13 8 602 16 9 592 12 10 586 16 11 59514 Session Average Size 593 SD Inter 8

Example 4

This experiment compares the average pore sizes of micron-size poresformed within a sheet or nozzle by means of a closed-loop feedbacksystem of the present invention and a prior art open-loop system. Thesystem used was an Excimer LASER with a wavelength of 308 nm. The opticssystem was a projection system, that simultaneously fabricated 6separate pore arrays. The beam from the LASER was split at thehomogenizer, and each beam had its own mechanical shutter. The shutterswere designed specifically for this application, and were actuated usingsolenoids. Below each of the 6 sheets were 6 separate Star Tech XR-16-GDetectors. When the power measured by a detector exceeded apredetermined threshold, the shutter for that beam was closed. When all6 pore arrays were fabricated, a new set of 6 sheets were moved intoposition, and the process was repeated. Under the ablation stage therewere six lenses that relayed the laser energy coming through the sheet(25 micro-meter thick polyimide film) onto six Star Tech sensors, theselenses were set at a 1 to 1 magnification with a focal plane about 2 mmabove the sensors. There was also an attenuator plate above the sensorsto cut the intensity into all the sensors.

Ten nozzle arrays were fabricated using a closed-loop drilling method(CL) and ten were fabricated using a similar open loop drilling Method(OL). For each time the sheets were positioned in the drilling area (1“pitch”), 6 nozzles or sheets (N1-N6) were drilled with each nozzlearray having an average of about 15 holes. For each drillingapplication, the following values are provided: average hole size(microns) per nozzle array, the standard deviation between nozzle arrayhole size averages for each pitch (PSD) and the standard deviation ofnozzle hole size averages from pitch to pitch (P/PSD). The standarddeviation between nozzle averages for each pitch (PSD) undergoing aclosed-loop drilling application was significantly lower than foropen-loop drilling applications. This is most dramatically demonstratedwhen comparing the pitch-to-pitch standard deviation P/PSD) for theclosed-loop drilling applications (PSD=0.04 micrometers) with those ofthe open-loop drilling applications (PSD=0.17 micrometers). Similarresults were found when performing a similar experiment for theformation of sub-micron size pores.

Pitch N1 N2 N3 N4 N5 N6 PSD Closed-Loop Application (all units aremicrometers) CL1 1.39 1.61 1.39 1.53 1.35 1.44 0.10 CL2 1.43 1.66 1.371.73 1.41 1.47 0.15 CL3 1.44 1.37 1.37 1.51 1.33 1.40 0.06 CL4 1.28 1.351.39 1.41 1.43 1.28 0.07 CL5 1.27 1.64 1.38 1.47 1.51 1.44 0.12 CL6 1.491.39 1.44 1.42 1.34 1.39 0.05 CL7 1.41 1.60 1.24 1.55 1.42 1.40 0.13 CL81.29 1.50 1.48 1.49 1.33 1.41 0.09 CL9 1.45 1.45 1.35 1.50 1.42 1.380.05 CL10 1.41 1.49 1.36 1.60 1.43 1.57 0.09 P/PSD 0.04 Open-LoopApplication (all units are micrometers) OL1 1.60 1.36 1.66 1.49 1.841.70 0.17 OL2 1.63 1.38 1.67 1.56 1.70 1.50 0.12 OL3 1.97 1.73 2.04 1.902.15 1.96 0.14 OL4 1.64 1.43 1.64 1.53 1.95 1.66 0.18 OL5 1.60 1.39 1.741.51 1.69 1.64 0.13 OL6 1.94 1.74 1.99 2.00 2.22 2.07 0.16 OL7 1.90 1.591.94 1.67 1.98 1.90 0.16 OL8 1.54 1.36 1.87 1.69 1.94 1.85 0.22 OL9 1.371.32 1.58 1.29 1.77 1.65 0.20 OL10 1.67 1.46 1.75 1.64 1.95 1.63 0.16P/PSD 0.17

The preceding merely illustrates the principles of the invention. Itwill be appreciated that those skilled in the art will be able to devisevarious arrangements which, although not explicitly described or shownherein, embody the principles of the invention and are included withinits spirit and scope. Furthermore, all examples and conditional languagerecited herein are principally intended to aid the reader inunderstanding the principles of the invention and the conceptscontributed by the inventors to furthering the art, and are to beconstrued as being without limitation to such specifically recitedexamples and conditions. Moreover, all statements herein recitingprinciples, aspects, and embodiments of the invention as well asspecific examples thereof, are intended to encompass both structural andfunctional equivalents thereof. Additionally, it is intended that suchequivalents include both currently known equivalents and equivalentsdeveloped in the future, i.e., any elements developed that perform thesame function, regardless of structure. The scope of the presentinvention, therefore, is not intended to be limited to the exemplaryembodiments shown and described herein. Rather, the scope and spirit ofpresent invention is embodied by the appended claims.

1. A method, comprising: directing light onto a polymer film, the lighthaving an intensity and a wavelength sufficient to form a pluralitypores within the sheet; forming a pore array within the sheet comprisinga plurality of pores at locations where the light contacts a surface ofthe sheet, wherein the light passes through the plurality of pores;detecting the light passing through the plurality of pores; analyzingthe detected light to determine if the plurality of pores meet a poresize and pore shape criterion; and moving formulation through the poresto create an aerosol.
 2. The method of claim 1, further comprising:inhaling the aerosol into lungs of a patient.
 3. The method of claim 1,further comprising: modifying the method based on whether the pore sizeand pore shape criterion is met.
 4. The method of claim 1, wherein thelight is a LASER.
 5. The method of claim 1, further comprising:repeating the directing, forming, detecting, and analyzing for each of aplurality of sheets.
 6. The method of claim 1, wherein each of theplurality of pores formed has a diameter of less than about 100 microns.7. The method of claim 4, wherein the LASER is selected from the groupconsisting of a UV LASER and a visible light LASER.
 8. The method ofclaim 1, wherein the detecting comprises using a detector selected fromthe group consisting of a photodiode, a pyroelectric detector and adownconversion/photodiode, and wherein the analyzing comprises using asystem comprising an electronic circuit.
 9. The method of claim 3,wherein the modifying comprises changing one or more of the intensity,the pulse duration, and the pulse frequency of the directed light. 10.The method of claim 9, wherein the modifying comprises reducing theintensity wherein the fabrication method is essentially halted.
 11. Themethod of claim 3, wherein the modifying comprises moving a new sheetinto the drilling position.
 12. The method of claim 7, wherein the UVLASER is selected from the group consisting of excimer LASERs, frequencymultiplied YAG LASERs, frequency multiplied YLF LASERs.
 13. The methodof claim 4, wherein the LASER is a pulsed Excimer LASER.